The present invention relates generally to methods and compositions for treating patients who have hepatic disease. More specifically, the present invention relates to an enteral composition specifically designed for patients with hepatic disease.
The liver, and its proper functioning, is of utmost importance to the survival of a patient. Because it is responsible for the metabolism of nearly all nutrients, and is the primary site for the inactivation of numerous toxins, the liver is one of the most important organs of the body. For example, the liver accounts for approximately 20% of the body's basal metabolism.
The liver extracts a majority of the amino acids, carbohydrates, lipids, vitamins, and minerals from portal circulation. These nutrients, extracted by the liver, are used as substrates or cofactors in all metabolic processes carried out in the liver. Synthesis of plasma proteins and bile secretion are additionally important processes carried out by the liver.
Due to a variety of insults and pathogens, the liver can become diseased. Liver disease is a broad classification encompassing a number of acute and chronic diseases. These diseases include: hepatitis (viral and non-viral); cirrhosis (alcoholic and non-alcoholic); and liver failure. Liver failure is perhaps the most severe disease and may be accompanied by a complex set of conditions including: hepatic encephalopathy; hemorrhage; coagulapathy; ascites; jaundice; and hepatorenal syndrome.
Although many medical treatments have been devised for treating liver disease, due to the paradoxical relationship between hepatic function and metabolism, medical treatment of the liver disease is complex and difficult. Most, if not all, liver diseases require or benefit from nutritional management. Those diseases which are believed to benefit most from nutritional management, include alcoholic and non-alcoholic cirrhosis, obstructive jaundice, and in some situations acute liver failure. The goals of such nutritional therapies vary depending on disease and patient. The goals can be either restorative or supportive.
Liver disease can affect both hepatic cellular function and structure. In chronic conditions such as alcoholic cirrhosis, exposure to a toxicant promotes inflammation of the periportal areas of the liver. As a result, fibrosis develops and when sufficiently advanced, canaliculi become blocked. As a result of inadequate regional perfusion, hepatocyte degeneration occurs.
In an attempt to restore adequate circulation, portal hypertension develops. Portosystemic shunting of the blood results in chronic hypertension. Many of the serious complications of liver disease are due to this event.
Portosystemic shunting allows many substances, for example, amino acids, fatty acids, ammonia, and others, to bypass the liver. These substances then flood the neurological system. Portosystemic shunting results in many clinical features including variceal changes and encephalopathy.
Many specific metabolic derangements are associated with liver disease. This is especially true of liver disease of a chronic nature. Such derangements include: increased plasma glucagon; hyperinsulinemia; increased plasma epinephrine and cortisol; decreased liver and muscle carbohydrate stores; accelerated gluconeogenesis; hypoglycemia; hyperammonemia; increased plasma aromatic amino acid; increased plasma methionine, glutamine, asparagine, and histidine; and decreased plasma branched chain amino acids.
A number of hypotheses, mostly metabolism based, have been advanced concerning the pathogenesis of hepatic encephalopathy. For example, excess nitrogen (ammonium) production and accumulation of false neural transmitters have been advanced as possible causes.
Although a number of nutritional formulations designed for hepatic patients had been proposed none of the formulations, in the opinion of the inventors, function entirely satisfactorily. Such formulations include: Amin-Aid.RTM. (Kendall-McGaw); and Travasorb.RTM. Hepatic (Clintec Nutrition Company).
One disadvantage with these formulations is that they are not ready to use. Rather, they are powders that require admixing and reconstitution before use. Powders that require admixing create disadvantages including sterility, labor, and time concerns.
Although a ready-to-use formulation would be desirable and greatly preferred over a powder, there are difficulties in attempting to create a ready-to-use formulations. The difficulties have, to the best of the inventors' belief, prevented the creation of viable ready-to-use hepatic enteral formulations. The difficulties include the instability of solutions containing free crystalline amino acids.
There is therefore a need for an improved nutritional formulation for patients with liver disease.